REGULATION OF COLLAGEN EXPRESSION AND CELL GROWTH IN FIBROPROLIFERATIVE DISEASES

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Our long term goal is to elucidate the normal wound healing process and abnormalities thereof that result in fibrotic diseases such as keloids , gingival hyperplasia and the gingival fibrosis of periodontal disease. To understand these fibroproliferative diseases, several of which occur at unusually high frequency in Black populations, we propose 1) to determine the level of specific fibrillar and nonfibrillar collagen types in normal and diseased gingival and dermal tissue and in fibroblast cultures derived from the tissues; and 2) to examine the effects of various modulators of inflammation and wound healing on cell growth and on the expression of various collagen types. The specific aims of the project are to: 1. Evaluate tissue and fibroblasts from normal gingiva and dermis with respect to expression of collagen types I,III,V,XII and type I trimer. 2. Extend the observations from Specific Aim 1, to involved tissues from patients with gingival hyperplasia, chronic periodontitis, and keloids, and to fibroblasts cultured from these tissues. 3. Determine the effects of various mediators of inflammation and tissue repair on cell growth and on the expression of the above collagen types. These will include the following mediators shown to regulate growth and collagen synthesis differently in normal and fibrotic tissue: hydrocortisone, transforming growth factor beta (TGFbeta), interleukin- 1(IL-1), phorbol ester tumor promotors and prostaglandin E2 (PGE2). 4. Determine the effects of Ca++ channel blockers that induce gingival hyperplasia on cell growth and collagen gene expression in fibroblasts from normal and fibrotic tissue in the presence and absence of mediators of inflammation. These studies may help to elucidate the role of specific mediators on growth and collagen synthesis during normal and abnormal wound healing, and to determine whether there are common elements in the etiology of gingival hyperplasia, the gingival fibrosis of chronic periodontal disease, and keloids.